Table 1.
The biological functions of interactions between KLHLs and different substrates
| KLHLs | Substrates | Degraded or not | Roles | References |
|---|---|---|---|---|
| KLHL2 | WNK4 | Yes | Anti-hypertension effect | [306] |
| WNK3 | Yes | Anti-hypertension effect | [331] | |
| NPCD | No | Regulation of neuronal development | [332] | |
| KLHL3 | WNK1 | Yes | Anti-hypertension effect | [333] |
| WNK4 | Yes | Anti-hypertension effect | [334-338] | |
| cMyBP-C | Yes | Regulation of heart development | [339] | |
| Claudin-8 | Yes | Anti-hypertension effect | [340] | |
| NCC | Yes | Anti-hypertension effect | [28] | |
| KLHL6 | HBXIP/Lamtor5 | No | Inhibition of B cell maturation | [341] |
| KLHL7 | TUT1 | Yes (K48) | Maintaining nucleolar integrity | [342] |
| KLHL8 | Rapsyn | Yes | Regulation of neuromuscular junction | [343] |
| KLHL9 | Aurora B | No | Regulation of Mitotic progression | [284] |
| IRS1 | Yes | Insulin resistance | [283] | |
| KLHL10 | dBruce | Yes | Regulation of spermiogenesis and male fertility | [344,345] |
| KLHL12 | DVLs | Yes | Inhibition of Wnt pathway | [140,141,147] |
| Lunapark | Yes | Regulation of neurodevelopment | [144] | |
| DRD4 | No | - | [346-348] | |
| SEC31 | No | Promotion of collagen secretion | [142,143] | |
| KHSRP | No | Inhibition of enterovirus ires-mediated translation | [349] | |
| KLHL13 | Aurora B | No | Regulation of mitotic progression | [284] |
| IRS1 | Yes | Insulin resistance | [283] | |
| KLHL15 | DCX, DCLK1 and DCLK2 | Yes | Regulation of neurogenesis | [350] |
| PP2A | Yes | Regulation of cellular dephosphorylation events | [351] | |
| CTIP | Yes | DNA-end resection and DSB repair | [352] | |
| KLHL16 | MAP1B-LC | Yes | Regulation of neuronal function | [161] |
| ATG16L1 | Yes (K48) | Regulation of autophagosomes production | [353] | |
| MAP8 | Yes | Regulation of neuronal function | [354] | |
| GFAF | Yes | Regulation of neuronal function | [162] | |
| TBCB | Yes | Regulation of neuronal function | [355] | |
| IFs | Yes | Regulation of neuronal function | [356] | |
| KLHL17 | GluR6 | Yes | Maintaining synaptic normality among neurons | [357] |
| KLHL18 | Aurora-A | Yes | Regulation of mitotic entry | [73] |
| UNC119 | Yes | Protection of cells from light damage | [358] | |
| KLHL19 | MCM3 | No | Maintaining the stability of cell cycle | [359,360] |
| PGAM5 | Yes | Regulation of oxidative stress | [361] | |
| PALB2 | No | Regulation of cell cycle | [362] | |
| P62 | No | Promotion of anti-oxidant response and autophagy | [363,364] | |
| MIRO-2 | Yes | Regulation of mitochondrial transport | [365] | |
| NRF1 | Yes | Cellular oxidative stress response | [237] | |
| NRF2 | Yes | Cellular oxidative stress response | [237] | |
| PGAM5, BCL2L1 | Yes | Promotion of cell apoptosis | [366] | |
| BCL2 | Yes | Promotion of cell apoptosis | [367] | |
| KLHL20 | Coronin 7 | No (K33) | Protein Trafficking | [368] |
| PDZ-RhoGEF | Yes | Neurite outgrowth | [369] | |
| DAPK, PML | Yes | Inhibition of apoptotic and autophagic death | [281] | |
| KLHL21 | EB | No | Promotion of cell migration | [370] |
| Aurora B | No | Regulation of mitosis | [371] | |
| KLHL22 | PLK1 | No | Regulation of mitosis | [98,372-374] |
| KLHL24 | KRT14 | Yes | Regulation of skin integrity | [375] |
| Keratin 14, 15 | Yes | Regulation of hair maintenance | [376] | |
| KLHL25 | 4E-BP1 | Yes | Promotion of translational activity | [377] |
| ACLY | Yes | Promotion of iTreg cell differentiation | [264] | |
| KLHL31 | FLNC | Yes | Maintenance of muscle function | [378] |
| KLHL38 | Myocardin | Yes | Promotion of heart failure | [67] |
| KLHL40 | DP | Yes | Regulation of skeletal muscle myogenesis | [379] |
| KLHL41 | Nebulin | No | Maintenance of muscle function | [380] |
| NRAP | Yes | Maintenance of muscle function | [381] | |
| KLHL42 | PPP2R5 | Yes | Promotion of connective tissue fibrosis | [382] |
| P60/Katanin | Yes | Regulation of mitosis | [383] |
Abbreviations: WNK1: WNK Lysine Deficient Protein Kinase 1; WNK3: WNK Lysine Deficient Protein Kinase 3; WNK4: WNK Lysine Deficient Protein Kinase 4; NPCD: Neuronal Pentraxin with Chromo Domain; cMyBP-C: Myosin Binding Protein C3; NCC: Na+-Cl- Cotransporter; HBXIP/Lamtor5: Late Endosomal/Lysosomal Adaptor; TUT1: Terminal Uridylyl Transferase 1; IRS1: Insulin Receptor Substrate 1; dBruce: One of the Inhibitor of Apoptosis Family of Proteins Family; DVLs: Disheveled Family Members; DRD4: Dopamine D4 Receptor; SEC31: Protein Transport Protein SEC31; KHSRP: KH-Type Splicing Regulatory Protein; DCX: Doublecortin; DCLK1: Doublecortin-Like Kinase 1; DCLK2: Doublecortin-Like Kinase 2; PP2A: Protein Phosphatase 2A; CTIP: Carboxy-Terminal Binding Protein 1 Interacting Protein; DSB: DNA Double Strand Breaks; MAP1B-LC: The Light Chain (LC) of Microtubule-Associated Protein 1B (MAP1B); ATG16L1: Autophagy Related 16 Like 1; MAP8: Microtubule-Associated Protein 8; GFAF: Glial Fibrillary Acidic Protein; TBCB: Tubulin Folding Cofactor B; IFs: Intermediate Filaments; GluR6: Glutamate Ionotropic Receptor Kainate Type Subunit 2; UNC119: Unc-119 Lipid Binding Chaperone; MCM3: Minichromosome Maintenance Complex Component 3; PGAM5: Phosphoglycerate Mutase Family Member 5; PALB2: Partner and Localizer of BRCA2; RHOT2/MIRO-2: Ras Homolog Family Member T2; NRF1: Nuclear Factor Erythroid-2-Related Factors 1; NRF2: Nuclear Factor Erythroid-2-Related Factors 2; BCL2L1: BCL2 Like 1; BCL2: BCL2 Apoptosis Regulator; PDZ-RhoGEF: Rho Guanine Nucleotide Exchange Factor 11 (also called ARHGEF11); DAPK: Death Associated Protein Kinase; PML: Promyelocytic Leukemia Protein; EB: End Binding Protein; PLK1: Polo Like Kinase 1; KRT14: Filamin-C (FlnC) Keratin 14; 4E-BP1: Eukaryotic Translation Initiation Factor 4E Binding Protein 1; ACLY: ATP-Citrate Lyase; iTreg: Inducible Regulatory T Cells; FLNC: Filamin C; DP: Dimerization Protein; NRAP: Nebulin-Related Anchoring Protein; PPP2R5: Phosphatase 2 Regulatory Subunit B’.